The role of the brain stem in GWVI pathology
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Principal Investigator: Ansgar J. Furst Organization: VETERANS ADMIN PALO ALTO HEALTH CARE SYS Fiscal Year: 2024 Funding agency: Veterans Affairs Gulf War Veterans’ Illness (GWVI) is characterized by multiple chronic symptoms including wide-spread pain and sleep disturbances. This project will focus on brainstem structures and white matter pathways that specifically link the hypothalamus, periaqueductal gray and locus coeruleus (along the hypothalamic-pituitary- adrenal axis), and investigate their role in modulating pain and sleep disturbances associated with GWVI. We hypothesize that GWVI is associated with damage of specific brainstem white matter circuits and nuclei known to modulate pain signaling and sleep-wake cycles resulting in dysregulation of these critical functions. We propose state-of-the-art brain imaging techniques to assess the brainstem fiber integrity and volume changes of key brainstem nuclei and correlate these imaging measures with GWVI-related pain and sleep measures, specifically. To test the novel hypothesis of pain modulation deficits in GWVI, we will additionally use conditioned pain modulation (CPM) to evaluate the efficacy of descending pain modulation stimulated by a noxious peripheral stimulus. The translation of our findings into new therapeutic trials is very probable given that there are several novel candidate interventions that would allow the targeting of these brainstem structures. Our hypotheses will be tested in an observational study comparing 50 GWVI Veterans and 50 non- symptomatic Gulf War era (GWE) Veterans. After screening, confirmation of eligibility, and consenting all Veterans will undergo a 2-day assessment. Day 1 will comprise a battery of cognitive / functional tests and a conditioned pain modulation (CPM) test. On Day 2, MRI exams will be performed on each patient and the remaining cognitive/functional testing will be completed. Both visits will be no more than one week apart. This 4-year proposal will include 100 participants (2 groups of 50 each) with outcome measures collected at appropriate time points. Terms: <Affect><Area><Atrophic><Atrophy><Body Tissues><Brain Stem><Brain imaging><Brainstem><Cell Nucleus><Chemicals><Chronic><Cognitive><Consent><Development><Dorsal><Drug usage><Eligibility><Eligibility Determination><Fiber><GW veteran><Gulf War><Gulf War Illness><Gulf War Syndrome><Gulf War veteran><HPA axis><Human><Hypothalamic structure><Hypothalamus><Image><Imaging Procedures><Imaging Technics><Imaging Techniques><Infectious Agent><Intervention><Intervention Strategies><Link><Locus Coeruleus><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measurement><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mefloquine><Mesencephalic Central Gray><Midbrain Central Gray><Modern Man><NMR Imaging><NMR Tomography><Neurologic><Neurological><Nuclear Magnetic Resonance Imaging><Nucleus><Nucleus Pigmentosus Pontis><Observation research><Observation study><Observational Study><Observational research><Operation Desert Shield><Operation Desert Storm><Organophosphates><Outcome Measure><Pain><Painful><Participant><Pathogenicity><Pathology><Pathway interactions><Patients><Periaqueductal Gray><Peripheral><Persian Gulf><Persian Gulf Syndrome><Probability><Process><Protocol Screening><Psychophysics><Psychotherapy><Reporting><Research><Research Design><Role><Severities><Skin><Sleep><Sleep Wake Cycle><Sleep disturbances><Stimulus><Stress><Structure><Study Type><Symptoms><Testing><Therapeutic Trials><Time><Tissues><Toxic effect><Toxicities><Translations><Veterans><Visit><Zeugmatography><aberrant sleep><annulus of the aqueduct><blue nucleus><brain visualization><burn pit><chronic symptom><conditioned pain modulation><determine efficacy><developmental><diagnostic criteria><disrupted sleep><disturbed sleep><drug use><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><gastrointestinal><hypothalamic><hypothalamic-pituitary-adrenal (HPA) axis><hypothalamic-pituitary-adrenal axis><hypothalmus-pituitary-adrenal axis><imaging><impaired sleep><infectious organism><interest><interventional strategy><irregular sleep><locus ceruleus structure><measurable outcome><midbrain central gray substance><neural imaging><neuro-imaging><neuroimaging><neurological imaging><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapeutics><new therapy><new therapy approaches><new treatment approach><new treatment strategy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapeutics><novel therapy><novel therapy approach><outcome measurement><pain processing><pain reduction><pain signal><pathway><periaqueductal gray matter><persistent symptom><psychophysical><pyridostigmine><reduce pain><respiratory><screening><screenings><sleep control><sleep disruption><sleep dysregulation><sleep regulation><social role><study design><substantia alba><symptomatology><translation><white matter>